Diffusion-weighted magnetic resonance imaging of the pancreas: diagnostic benefit from an intravoxel incoherent motion model-based 3 b-value analysis.

OBJECTIVES: The objective of this study was to evaluate the diagnostic benefit of an intravoxel incoherent motion (IVIM) model-based characterization of pancreatic masses from diffusion-weighted imaging (DWI) with 3 b values. MATERIALS AND METHODS: This retrospective study had an approval from the institutional review board, and informed patient consent was waived. The 1.5-T DWI data of 42 patients with or without pancreatic disease, acquired by a respiratory-gated spin-echo echo-planar imaging sequence with 3 b values (0, 50, 800 s/mm²), were retrospectively analyzed. The IVIM-related parameters D', which is the apparent diffusion coefficient [ADC(50,800)], and f', as well as ADC(0,50), and conventional ADC(0,800) were calculated voxelwise. Regions of interest were analyzed in pancreatic adenocarcinomas (CAs, n = 12), neuroendocrine pancreatic tumors (NETs, n = 9), and chronic pancreatitis (CPs, n = 11), not affected tissue of each pathologic group, and in the head, body, and tail of the healthy pancreas (n = 10). RESULTS: By ADC(0,800) and D', CAs could hardly be distinguished from neuroendocrine pancreatic tumors and chronic pancreatitis. However, CAs revealed very low ADC(0,50) and f' values, which differed significantly from all other groups. In the healthy pancreas, ADC(0,800) and D' values were significantly higher for the head than for the body and tail, but no significant differences were found for ADC(0,50) and f'. CONCLUSIONS: The determination of IVIM-based microcirculation-sensitive parameter maps from DWI with 3 b values significantly improved the discrimination of CAs from NETs, CPs, and the healthy tissue.

Drug nanocarriers labeled with near-infrared-emitting quantum dots (quantoplexes): imaging fast dynamics of distribution in living animals.

The knowledge of the biodistribution of macromolecular drug formulations is a key to their successful development for specific tissue- and tumor-targeting after systemic application. Based on the polyplex formulations, we introduce novel drug nanocarriers, which we denote as "quantoplexes" incorporating near-infrared (IR)-emitting cadmium telluride (CdTe) quantum dots (QDs), polyethylenimine (PEI), and a macromolecular model drug [plasmid DNA (pDNA)], and demonstrate the ability of tracking these bioactive compounds in living animals. Intravenous application of bare QD into nude mice leads to rapid accumulation in the liver and peripheral regions resembling lymph nodes, followed by clearance via the liver within hours to days. Quantoplexes rapidly accumulate in the lung, liver, and spleen and the fluorescent signal is detectable for at least a week. Tracking quantoplexes immediately after intravenous injection shows rapid redistribution from the lung to the liver within 5 minutes, depending on the PEI topology and quantoplex formulation used. With polyethyleneglycol (PEG)-modified quantoplexes, blood circulation and passive tumor accumulation was measured in real time. The use of quantoplexes will strongly accelerate the development of tissue and tumor-targeted macromolecular drug carriers.

Hyperthermia-induced targeting of thermosensitive gene carriers to tumors.

Locoregional hyperthermia (HT) can be used for site-directed activation of macromolecular drug delivery systems. We have developed a gene delivery system based on thermosensitive block copolymers (TSCs) with a phase transition temperature of 42 degrees C [Zintchenko, A., Ogris, M., and Wagner, E. (2006). Bioconjug. Chem. 17, 766-772], in which the statistical copolymer of vinylpyrrolidinone and N-isopropylacryamide is grafted on polyethylenimine (PEI). Here we applied polyplexes consisting of plasmid DNA and TSCs systemically in A/J mice bearing a syngeneic Neuro2A neuroblastoma tumor subcutaneously in each hind limb. One limb was selectively treated by HT at 42 degrees C, at the same time that polyplexes were injected via the tail vein. Hyperthermia led to increased accumulation of thermosensitive polymer and aggregation of thermosensitive polyplexes in HT-treated tumors, resulting in up to 10-fold increased DNA deposition compared with non-HT-treated tumor. The level of transgene expression induced by TSC polyplexes in HT-treated tumors was significantly higher and selective for tumor tissue. With nonthermosensitive PEI polyplexes HT did not influence transgene deposition or expression in tumor.